1wci

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[[Image:1wci.gif|left|200px]]
[[Image:1wci.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1wci |SIZE=350|CAPTION= <scene name='initialview01'>1wci</scene>, resolution 1.84&Aring;
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The line below this paragraph, containing "STRUCTURE_1wci", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Mn+Binding+Site+For+Chain+A'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=WWF:C2-1-HYDROXY-3-METHYL-BUTYL-THIAMIN'>WWF</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/3-methyl-2-oxobutanoate_dehydrogenase_(2-methylpropanoyl-transferring) 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.4 1.2.4.4] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1wci| PDB=1wci | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wci OCA], [http://www.ebi.ac.uk/pdbsum/1wci PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wci RCSB]</span>
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}}
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'''REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH'''
'''REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH'''
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==Reference==
==Reference==
A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase., Machius M, Wynn RM, Chuang JL, Li J, Kluger R, Yu D, Tomchick DR, Brautigam CA, Chuang DT, Structure. 2006 Feb;14(2):287-98. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16472748 16472748]
A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase., Machius M, Wynn RM, Chuang JL, Li J, Kluger R, Yu D, Tomchick DR, Brautigam CA, Chuang DT, Structure. 2006 Feb;14(2):287-98. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16472748 16472748]
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[[Category: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Tomchick, D R.]]
[[Category: Tomchick, D R.]]
[[Category: Wynn, R M.]]
[[Category: Wynn, R M.]]
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[[Category: acylation]]
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[[Category: Acylation]]
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[[Category: branched-chain,multi enzyme complex]]
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[[Category: Branched-chain,multi enzyme complex]]
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[[Category: conformational switch]]
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[[Category: Conformational switch]]
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[[Category: flavoprotein]]
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[[Category: Flavoprotein]]
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[[Category: ketoacid dehydrogenase]]
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[[Category: Ketoacid dehydrogenase]]
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[[Category: maple syru urine disease]]
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[[Category: Maple syru urine disease]]
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[[Category: maple syrup urine disease]]
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[[Category: Maple syrup urine disease]]
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[[Category: mitochondrion]]
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[[Category: Mitochondrion]]
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[[Category: oxidative decarboxylation]]
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[[Category: Oxidative decarboxylation]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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[[Category: phosphorylation]]
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[[Category: Phosphorylation]]
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[[Category: reactivity]]
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[[Category: Reactivity]]
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[[Category: thiamine]]
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[[Category: Thiamine]]
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[[Category: thiamine diphosphate]]
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[[Category: Thiamine diphosphate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:27:53 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:34:22 2008''
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Revision as of 10:27, 3 May 2008

Image:1wci.gif

Template:STRUCTURE 1wci

REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH


Overview

The dehydrogenase/decarboxylase (E1b) component of the 4 MD human branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) is a thiamin diphosphate (ThDP)-dependent enzyme. We have determined the crystal structures of E1b with ThDP bound intermediates after decarboxylation of alpha-ketoacids. We show that a key tyrosine residue in the E1b active site functions as a conformational switch to reduce the reactivity of the ThDP cofactor through interactions with its thiazolium ring. The intermediates do not assume the often-postulated enamine state, but likely a carbanion state. The carbanion presumably facilitates the second E1b-catalyzed reaction, involving the transfer of an acyl moiety from the intermediate to a lipoic acid prosthetic group in the transacylase (E2b) component of the BCKDC. The tyrosine switch further remodels an E1b loop region to promote E1b binding to E2b. Our results illustrate the versatility of the tyrosine switch in coordinating the catalytic events in E1b by modulating the reactivity of reaction intermediates.

About this Structure

1WCI is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase., Machius M, Wynn RM, Chuang JL, Li J, Kluger R, Yu D, Tomchick DR, Brautigam CA, Chuang DT, Structure. 2006 Feb;14(2):287-98. PMID:16472748 Page seeded by OCA on Sat May 3 13:27:53 2008

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